Aminoalkyl-substituted heterocycles

ABSTRACT

Racemic or optically active compounds of the formula 
     
         Q--C.sub.n H.sub.2n --NH--R 
    
     wherein Q is ##STR1## where R 1  is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino, 
     R 2  is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or trifluoromethyl, or 
     R 1  and R 2 , together with each other, are methylenedioxy or ethylenedioxy; 
     n is an integer from 2 to 6, inclusive; and 
     R is hydrogen, benzyl or ##STR2## and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as vasodilators and CNS-stimulators.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. Patent Application Ser. No. 102,904, filed Dec. 13, 1979, now U.S. Pat. No. 4,271,158, which in turn is a divisional of U.S. Patent Application Ser. No. 026,608, filed Apr. 3, 1979, now U.S. Pat. No. 4,215,119, which in turn is a continuation-in-part of copending U.S. patent application Ser. No. 773,394 filed Mar. 2, 1977, now U.S. Pat. No. 4,154,829, incorporated herein by reference.

This invention relates to novel aminoalkyl-substituted heterocycles and non-toxic salts thereof, as well as to various methods of preparing these compounds.

More particularly, the present invention relates to a novel class of aminoalkyl-substituted heterocycles represented by the formula

    Q--C.sub.n H.sub.2n --NH--R

(I)

wherein Q is ##STR3## where

R₁ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino,

R₂ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or trifluoromethyl,

R₁ and R₂, together with each other, are methylenedioxy or ethylenedioxy, and

A is --O--, --CH₂ --CH₂ --, or --NR₃ -- where R₃ is hydrogen or alkyl of 1 to 4 carbon atoms,

n is an integer from 2 to 6, inclusive, and

R is hydrogen, benzyl or ##STR4## where

R₄ is hydrogen, methyl or ethyl,

R₅, R₆ and R₇, which may be identical to or different from each other, are each hydrogen, halogen, hydroxymethyl, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro, cyano, --CONHR₃, --CONHOH, --COOR₃, R₈ O--, methylsulfonylmethyl or, when one or two of R₅ through R₇ are other than halogen

r trifluoromethyl, also --NR₃ R₉,

where

R₃ has the meanings defined above, R₈ is hydrogen, alkanoyl of 1 to 20 carbon atoms, alkyl of 1 to 4 carbon atoms or aralkyl, and

R₉ is hydrogen, lower alkanoyl, methanesulfonyl, carbamoyl, dimethylsulfamoyl, or alkoxycarbonyl of 2 to 5 carbon atoms, and

R₅ and R₆, together with each other, are --O--CH₂ --O, --O--CH₂ --CH₂ --O--, --CH═CH--CH═CH--, --O--CH₂ --CONH--, --CH₂ --CH₂ --CONH-- or --O--CO--NH--,

and non-toxic, pharmacologically acceptable acid addition salts thereof.

The alkylene chain --C_(n) H_(2n) -- in formula I may be straight or branched, and preferred ebodiments thereof are --CH₂ --CH₂ --, --CH₂ --CH₂ --CH₂ --, --CH₂ --C(CH₃)₂ -- and primarily --CH₂ --CH₂ --C(CH₃)₂ --, where the tertiary carbon atom is bonded to the nitrogen atom or the --NH--R moiety.

A subgenus thereunder is constituted by compounds of the formula I, wherein

Q, A and R₃ have the meanings previously defined,

R₁ is hydrogen, methoxy or amino,

R₂ is hydrogen or methoxy,

n is an integer from 3 to 6, inclusive, R is hydrogen or ##STR5##

R₅ is hydrogen, --OR₈, --NHR₉, hydroxymethyl, cyano, --CONHR₃ or halogen,

R₆ is hydrogen, hydroxyl or halogen,

R₇ is hydrogen, chlorine, methyl or methoxy,

R₈ is hydrogen, benzyl, methyl or alkanoyl, and

R₉ is hydrogen, formyl, acetyl, methylsulfonyl, carbamoyl or dimethylsulfamoyl,

provided that, when R₆ and/or R₇ are halogen, R₅ is other than --NHR₉ ; and non-toxic, pharmacologically acceptable acid addition salts thereof.

A particularly preferred subgenus thereunder is constituted by compounds of the formula I, wherein

Q, A, R₃, R₄ and n have the meanings previously defined,

R₁ is hydrogen, methoxy or amino,

R₂ is hydrogen or methoxy,

R is hydrogen or ##STR6##

R₅ is hydrogen or hydroxyl,

R₆ is hydrogen, hydroxyl, hydroxymethyl, cyano, --CONHR₃, --OR₃ or chlorine,

R₅ and R₆, together with each other, are --CH═CH--CH═CH--, --OCH₂ --CONH--, --CH₂ --CH₂ --CONH-- or --O--CONH--,

R₇ is hydrogen, methyl, methoxy, hydroxyl or chlorine, and

R₃ is hydrogen, benzyl or lower alkanoyl, and non-toxic, pharmacologically acceptable acid addition salts thereof.

The compounds embraced by formula I may be prepared by the following methods, all of which involve known organic synthesis priniples:

METHOD A

For the preparation of a compound of the formula I wherein R is a grouping of the formula III, by reacting an amine of the formula

    Q--C.sub.n H.sub.2n --NH.sub.2

(IV)

wherein Q and n have the same meanings as in formula I, with a compound of the formula ##STR7## wherein

R₅, R₆ and R₇ have the same meanings as in formula I, and

R₁₀ is hydrogen or alkyl, under reductive amination conditions. Suitable reducing agents are complex hydrides, preferably sodium borohydride, or hydrogen in the presence of a hydrogenation catalyst, preferably platinum, palladium or nickel.

METHOD B

For the preparation of a compound of the formula I wherein R is a grouping of the formula III, by reducing a compound of the formula ##STR8## wherein Q, n, R₄, R₅, R₆ and R₇ have the same meanings as in formula I, with a complex hydride, in particular sodium borohydride, or by catalytic hydrogenation with a conventional hydrogenation catalyst, for example, platinum, palladium or nickel.

METHOD C

For the preparation of a compound of the formula I, wherein R is a grouping of the formula III, by reacting an epoxide of the formula ##STR9## wherein R₄, R₅, R₆ and R₇ have the same meanings as in formula I, with an amine of the formula IV; or by reacting a halohydrin of the formula ##STR10## wherein

R₄, R₅, R₆ and R₇ have the same meanings as in formula I, and

Hal is halogen,

with an amine of the formula IV in the presence of an acid binding agent, such as potassium carbonate, sodium carbonate or an excess of the amine IV. The halohydrin of the formula VIII converts into the corresponding epoxide VII under the reaction conditions.

METHOD D

For the preparation of a compound of the formula I wherein --C_(n) H_(2n) -- is ##STR11## where

n has the same meanings as in formula I, and

R₁₁ is hydrogen or methyl, by reductive amination of a compound of the formula ##STR12## wherein

Q and n have the same meanings as in formula I, and

R₁₁ has the meanings defined above, with an amine of the formula

    H.sub.2 N--R                                               (X)

wherein R has the same meanings as in formula I. Suitable reducing agents are complex hydrides, such as sodium borohydride, or hydrogen in the presence of a catalyst, such as platinum, palladium or nickel; or by reducing a compound of the formula ##STR13## wherein Q, n, R₄ and R have the meanings previously defined.

METHOD E

For the preparation of a compound of the formula I wherein R is a grouping of the formula III, by removing the --CH₂ --aryl protective group from a compound of the formula ##STR14## wherein Q, n, R₄, R₅, R₆ and R₇ have the same meanings as in formula I, by catalytic hydrogenation with a catalyst such as platinum, palladium or nickel.

METHOD F

For the preparation of a compound of the formula I in which at least one of substituents R₅, R₆ and R₇ is hydroxyl, by removing the arylmethyl protective group or groups from a corresponding compound wherein the respective hydroxyl substituent or substituents are arylmethylated. The removal of the arylmethyl group or groups is effected by catalytic hysdrogenation with a catalyst such as platinum, palladium or nickel, or by ether cleavage with a hydrohalic acid or boron tribromide.

METHOD G

For the preparation of a compound of the formula I wherein R₅ is --NH--acyl or --NH--CO--NH₂, by reacting a compound of the formula ##STR15## wherein

Q, n, R₄, R₆ and R₇ have the same meanings as in formula I, and

X is an anion,

with a carboxylic acid anhydride for introduction of the acyl radical, or with a cyanate and an acid for introduction of the carbamoyl radical. At least one mol of an acid, which protects the secondary amino group by salt formation, is additionally required.

METHOD H

For the preparation of a compound of the formula I wherein R₅ is --CONHR₃, --CONHNH₂ or --CONHOH, by reacting an ester of the formula ##STR16## wherein

Q, n, R₄, R₆ and R₇ have the same meanings as in formula I, and

R" is alkyl or substituted alkyl, with a compound of the formula

    NH.sub.2 --R.sub.12                                        (XV)

wherein R₁₂ is hydrogen, lower alkyl, hydroxyl or amino.

METHOD I

For the preparation of a compound of the formula I wherein R is hydrogen or benzyl, by removing the protective group or groups from a compound of the formula ##STR17## wherein

Q and n have the same meanings as in formula I,

R₁₃ is arylmethyl, acryl or --COOR₁₅,

R₁₄ is hydrogen or benzyl, and

R₁₃ and R₁₄, together with each other, are a dicarboxylic acid radical, such as succinyl or phthalyl, or --CHR₁₅ --,

where R₁₅ is alkyl, arylmethyl or aryl.

When R₁₃ is acyl or --COOR₁₅, or R₁₃ and R₁₄ together are a dicarboxylic acid radical or --CHR₁₅ --, the protective groups are removed by hydrolysis. When R₁₃ and R₁₄ together are a dicarboxylic acid radical, such as phthalyl, the removal may be effected by ring cleavage with hydrazine, followed by hydrolysis. When R₁₃ and/or R₁₄ are arylmethyl, the removal must be effected by hydrogenation in the presence of a catalyst, such as platinum, palladium or nickel. It is also possible to remove the protective group by catalytic hydrogenation when R₁₅ in --COOR₁₅ is arylmethyl.

METHOD J

For the preparation of a compound of the formula I wherein R is hydrogen, by reducing the nitro group in a compound of the formula

    Q--C.sub.n H.sub.2n --NO.sub.2                             (XVII)

wherein Q and n have the same meanings as in formula I, preferably by catalytic hydrogenation with conventional catalysts, such as nickel.

The starting compounds for methods A through J are either known compounds or may be prepared by known methods.

In those instances where the end products of methods A through J are racemates, these may be separated into the optical antipode components by conventional methods.

The compounds embraced by formula I are organic bases and therefore form acid addition salts with inorganic or organic acids. Examples of non-toxic, pharmacologically acceptable acid addition salts are those formed with hydrochloric acid, hydrobromic acid, sulfuric acid, maleic acid, succinic acid, formic acid, p-amino-benzoic acid, methanesulfonic acid, 8-chlorotheophylline or the like.

The following examples illustrate the present invention and will enable others skilled in the art to understand it more completely. It should be understood, however, that the invention is not limited solely to the particular examples given below.

EXAMPLE I

A mixture consisting of 5.36 gm of 3,4-dichlorophenyl-glyoxal hydrate, 4.5 gm of 1-(3-amino-n-propyl)-1,2,3,4-tetrahydro-quinolone-(2) and 200 ml of ethanol was heated at 50° C. for 1 hour. Then, while cooling, it was admixed with 5 gm of sodium borohydride at 0° to 5° C., the mixture was stirred for 2 hours at room temperature and then acidified with hydrochloric acid, the ethanol was distilled off, and the residue was made alkaline with ammonia. 5.5 gm of the free base, m.p. 95° C., of the formula ##STR18## were obtained. Its hydrochloride, m.p. 185° C., was obtained by admixing the free base with the calculated amount of ethereal hydrochloric acid.

EXAMPLE 2

A mixture consisting of 11 gm of 1-(3,4-dibenzyloxyphenyl)-1-oxo-2-hydroxy-2-ethoxyethane (m.p.114° C.), 5.6 gm of 1-(3,3-dimethyl-3-amino-n-propyl)-benzimidazolinone-(2) and 225 ml of ethanol was heated for 3 hours and subsequently admixed at 0° to 5° C. with 8 gm of sodium borohydride. The resulting solution was allowed to stand at room temperature for 12 hours, and then acidified with hydrochloric acid and worked up as described in the preceeding example. 12.7 gm of free base, m.p. 130° C., of the formula ##STR19## were obtained. Its maleate, m.p. 197° C., was obtained by adding a solution of maleic acid in acetonitrile to the base.

Using procedures and starting compounds analogous to those described in Examples 1 and 2, the compounds shown in the following table were also prepared. The indicated yields are in % of theory.

                                      TABLE I                                      __________________________________________________________________________     Ex.                                       Yield %                                                                             M.P. of    m.p. of              No.                                                                               Formula                                of theory                                                                           Base °C.                                                                     Salt  Salt                 __________________________________________________________________________                                                               °C.               ##STR20##                             82   115                             4                                                                                  ##STR21##                             66        maleate                                                                              134                  5                                                                                  ##STR22##                             81        maleate                                                                              217                  6                                                                                  ##STR23##                             78   151                             7                                                                                  ##STR24##                             79        succinate                                                                             94                  8                                                                                  ##STR25##                             88        p-amino- benzoate                                                                    166                  9                                                                                  ##STR26##                             60    93                             10                                                                                 ##STR27##                             75   170  methane- sulfonate                                                                   185                  11                                                                                 ##STR28##                             78   amor- phous                     12                                                                                 ##STR29##                             74        hydro- chloride                                                                      194                  13                                                                                 ##STR30##                             88        hydro- chloride                                                                      215                  14                                                                                 ##STR31##                             84        maleate                                                                              209                  15                                                                                 ##STR32##                             66        succinate                                                                            168                  16                                                                                 ##STR33##                             66        sulfate                                                                              250                  17                                                                                 ##STR34##                             88   135                             18                                                                                 ##STR35##                             66   126                             19                                                                                 ##STR36##                             69.5 134                             20                                                                                 ##STR37##                             72        hydro- chloride                                                                      252                  21                                                                                 ##STR38##                             87        sulfate                                                                              225                  22                                                                                 ##STR39##                             80        p-amino- benzoate                                                                    123                  23                                                                                 ##STR40##                             68        sulfate                    24                                                                                 ##STR41##                             82        hydro- chloride                                                                      215                  25                                                                                 ##STR42##                             93    93                             26                                                                                 ##STR43##                             82        sulfate                                                                              183                  27                                                                                 ##STR44##                             80    68                             28                                                                                 ##STR45##                             61        maleate                                                                              137                  29                                                                                 ##STR46##                             81        maleate                                                                              123                  30                                                                                 ##STR47##                             70        hydro- chloride                                                                      193                  31                                                                                 ##STR48##                             78        p-amino- benzoate                                                                    118                  32                                                                                 ##STR49##                             73   178  maleate                                                                              161                  33                                                                                 ##STR50##                             62        succinate                                                                            198                  34                                                                                 ##STR51##                             81   139  succinate                                                                            206                  35                                                                                 ##STR52##                             75   141  maleate                                                                              218                  36                                                                                 ##STR53##                             69        maleate                                                                              168                  37                                                                                 ##STR54##                             83        hydro- chloride                                                                      196                  38                                                                                 ##STR55##                             67        succinate                                                                            180                  39                                                                                 ##STR56##                             84        maleate                                                                              170                  40                                                                                 ##STR57##                             69        hydro- chloride                                                                      170                  41                                                                                 ##STR58##                             79        hydro- chloride                                                                      116                  42                                                                                 ##STR59##                             70        maleate                                                                              210                  43                                                                                 ##STR60##                             68        hydro- chloride                                                                      209                  44                                                                                 ##STR61##                             50        p-amino- benzoate                                                                    152,5                45                                                                                 ##STR62##                             53        p-amino- benzoate                                                                    159                  46                                                                                 ##STR63##                             38   163  hydro- chloride                                                                      148                  47                                                                                 ##STR64##                             86        hydro-  chloride                                                                     183                  48                                                                                 ##STR65##                             88.5 116                             49                                                                                 ##STR66##                             95,4 122                             50                                                                                 ##STR67##                             84,5      hydro- chloride                                                                      197                  51                                                                                 ##STR68##                             86        hydro- chloride                                                                      142                  52                                                                                 ##STR69##                             83        hydro- chloride                                                                      176                  53                                                                                 ##STR70##                             77   107                             54                                                                                 ##STR71##                             64        hydro- chloride                                                                      233                  55                                                                                 ##STR72##                             75        maleate                                                                              218                  56                                                                                 ##STR73##                             70.3      hydro- chloride                                                                      196                  57                                                                                 ##STR74##                             70.3      hydro- chloride                                                                      181                  58                                                                                 ##STR75##                             62        sulfate                                                                              259                  59                                                                                 ##STR76##                             89   122  hydro- chloride                                                                      172                  60                                                                                 ##STR77##                             87   108  maleate                                                                              242                  61                                                                                 ##STR78##                             83   127   hydro- chloride                                                                     220                  62                                                                                 ##STR79##                             88   137  methane- sulfonate                                                                   170                  63                                                                                 ##STR80##                             79   183  hydro- chloride                                                                      198                  64                                                                                 ##STR81##                             68   116  sulfate                                                                              248                  65                                                                                 ##STR82##                             86        Formate                                                                              143                  66                                                                                 ##STR83##                             78   112- 114                                                                            hydro- chloride                                                                .H.sub.2 O                                                                           227- 228             67                                                                                 ##STR84##                             71    84                             68                                                                                 ##STR85##                             73        hydro- chloride                                                                      197                  69                                                                                 ##STR86##                             79   168  maleate                                                                               88                  70                                                                                 ##STR87##                             73        hydro- chloride                                                                      187                  71                                                                                 ##STR88##                             69        hydro- chloride                                                                      decomp.                                                                        >200°         72                                                                                 ##STR89##                                                                  73                                                                                 ##STR90##                                                                  74                                                                                 ##STR91##                                                                  75                                                                                 ##STR92##                                                                  76                                                                                 ##STR93##                                                                  77                                                                                 ##STR94##                                                                  78                                                                                 ##STR95##                                                                  79                                                                                 ##STR96##                                                                  80                                                                                 ##STR97##                                                                  81                                                                                 ##STR98##                                                                  82                                                                                 ##STR99##                                                                  83                                                                                 ##STR100##                                                                 __________________________________________________________________________

EXAMPLE 84

A mixture consisting of 42.5 gm of 3,4-dibenzyloxyphenyl-ω-bromoacetophenone, 29 gm of N-methyl-N'-(2-benzylamino-ethyl)-benzimidazolinone-(2), 25 gm of sodium carbonate and 600 ml of acetonitrile was refluxed for 2 hours. Thereafter, the precipitated inorganic products were filtered off, and the solvent was distilled out of the filtrate under a water aspirator vacuum in a rotary evaporator, the residue was taken up in 900 ml of methanol, 30 ml of an ethereal 12% hydrochloric acid solution and 15 ml of an ethereal 1% palladium chloride solution were added, and the mixture was hydrogenated in the presence of 2 gm of activated charcoal at 60° C. and 6 atmospheres until 3 molar equivalents of hydrogen had been absorbed. After separation of the catalyst, about half of the methanol was distilled off, and the residual solution was admixed with 500 ml of acetonitrile. 32 gm of 1-(3,4-dihydroxyphenyl)-1-oxo-2-[(3-methyl)-benzimidazolinone-(2)-yl]-ethylaminoethane hydrochloride crystallized out which after recrystallization from water, had a melting point of 250° C. 8 gm of this aminoketone were hydrogenated in 400 ml of methanol in the presence of 1 gm of platinum oxide under standard conditions until 1 molar equivalent of hydrogen had been absorbed, and the hydrogenation product was isolated as its hydrochloride of the formula ##STR101## having a melting point of 185° C. The yield was 88% of theory.

Using an analogous procedure and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE II                                     __________________________________________________________________________     Ex.                                      Yield %                                                                             m.p. of     m.p. of              No. Formula                              of theory                                                                           Base °C.                                                                     Salt   Salt                 __________________________________________________________________________                                                               °C.           85                                                                                  ##STR102##                          89        p-amino- benzoate                                                                     161                  86                                                                                  ##STR103##                          92        maleate                                                                               134                  87                                                                                  ##STR104##                          92        maleate                                                                               209                  88                                                                                  ##STR105##                          93        succinate                                                                             168                  89                                                                                  ##STR106##                          90        maleate                                                                               168                  90                                                                                  ##STR107##                          96        maleate                                                                               210                  91                                                                                  ##STR108##                          93        hydrochloride                                                                         239                  92                                                                                  ##STR109##                          94        p-amino- benzoate                                                                     159                  93                                                                                  ##STR110##                          88        hydrochloride                                                                         170                  94                                                                                  ##STR111##                          89        succinate                                                                             204                  95                                                                                  ##STR112##                          78        cyclamate                                                                             176                  96                                                                                  ##STR113##                          93   170  methane- sulfonate                                                                    185                  97                                                                                  ##STR114##                          90        maleate                                                                               138                  98                                                                                  ##STR115##                          94        maleate H.sub.2                                                                       180                  99                                                                                  ##STR116##                          85        maleate                                                                               157                  100                                                                                 ##STR117##                          92        maleate                                                                               180                  101                                                                                 ##STR118##                          90        hydrochloride .2H.sub.2                                                         O     275                  102                                                                                 ##STR119##                          94        hydrochloride                                                                         265                  103                                                                                 ##STR120##                          93        hydrochloride                                                                         177                  104                                                                                 ##STR121##                          89        succinate                                                                             215                  105                                                                                 ##STR122##                          92        succinate .H.sub.2                                                                    128                  106                                                                                 ##STR123##                          94        p-amino- benzoate                                                                     166                  107                                                                                 ##STR124##                          91        succinate                                                                             169-71               108                                                                                 ##STR125##                          90        p-amino benzoate                                                                      193                  109                                                                                 ##STR126##                          84        succinate                                                                             176                  110                                                                                 ##STR127##                          90   212  p-amino- benzoate                                                                     234                  111                                                                                 ##STR128##                          92   148  p-amino- benzoate                                                                     191                  112                                                                                 ##STR129##                          90        hydrochloride                                                                         190                  113                                                                                 ##STR130##                          89        succinate                                                                             189                  114                                                                                 ##STR131##                          90        Formiate 1/2 CH.sub.3                                                          CN     159                  115                                                                                 ##STR132##                          93   95   hydrochloride                                                                         185                  116                                                                                 ##STR133##                          94        hydrochloride                                                                         198                  117                                                                                 ##STR134##                          93        p-amino- benzoate                                                                     199                  118                                                                                 ##STR135##                          90        hydrochloride                                                                         175                  119                                                                                 ##STR136##                          91   206  hydrochloride                                                                         169                  120                                                                                 ##STR137##                          94   200  hydrochloride                                                                         201                  121                                                                                 ##STR138##                          85   198  hydrochloride                                                                         157                  122                                                                                 ##STR139##                          92        succinate                                                                             198                  123                                                                                 ##STR140##                          89        acid maleate                                                                          202                  124                                                                                 ##STR141##                          97        acid maleate                                                                          180                  125                                                                                 ##STR142##                          92        acid maleate                                                                          168                  126                                                                                 ##STR143##                          89        hydrochloride                                                                         230                  127                                                                                 ##STR144##                          94        hydrochloride                                                                         252                  128                                                                                 ##STR145##                          90        succinate                                                                             173                  129                                                                                 ##STR146##                          91   198  hydrochloride                                                                         235                  130                                                                                 ##STR147##                          84        succinate                                                                             212                  131                                                                                 ##STR148##                          89        succinate                                                                             218                  132                                                                                 ##STR149##                          94   180  hydrochloride                                                                         190                  133                                                                                 ##STR150##                          88        formate                                                                               214                  134                                                                                 ##STR151##                          92   190  hydrochloride                                                                         225                  135                                                                                 ##STR152##                          87        hydrochloride                                                                         170                  136                                                                                 ##STR153##                          90   193  hydrochloride                                                                         196                  137                                                                                 ##STR154##                          96        maleate                                                                               210                  138                                                                                 ##STR155##                          96        hydrochloride                                                                         239                  139                                                                                 ##STR156##                          93        p-amino-  benzoate                                                                    152.5                140                                                                                 ##STR157##                          90        p-amino- benzoate                                                                     159                  141                                                                                 ##STR158##                          67   163  hydrochloride                                                                         148                  142                                                                                 ##STR159##                          81        p-amino- benzoate                                                                     190                  143                                                                                 ##STR160##                          79        hydrochloride                                                                         262                  144                                                                                 ##STR161##                          84        maleate                                                                               202                  145                                                                                 ##STR162##                          88        maleate                                                                               202                  146                                                                                 ##STR163##                          85   180  succinate                                                                             203                  147                                                                                 ##STR164##                          88        p-amino- benzoate                                                                     196                  148                                                                                 ##STR165##                          90   180  hydrochloride                                                                         193                  149                                                                                 ##STR166##                          72        hydrochloride                                                                         212                  150                                                                                 ##STR167##                          69        hydrochloride                                                                         182                  151                                                                                 ##STR168##                          76        hydrochloride                                                                         221                  152                                                                                 ##STR169##                          82   113  hydrochloride .H.sub.2                                                         O      80-82                153                                                                                 ##STR170##                          79        formate                                                                               138                  154                                                                                 ##STR171##                          72        methanesul- fonate.H.su                                                        b.2 O  120                  155                                                                                 ##STR172##                          76        hydrochloride                                                                         252                  156                                                                                 ##STR173##                          81        sulfate                                                                               192                  157                                                                                 ##STR174##                          72        hydrochloride                                                                         209                  158                                                                                 ##STR175##                                    hydro- chloride                                                                .H.sub.2 O                                                                            173-176              159                                                                                 ##STR176##                          83        hydro- chloride                                                                       amorphous            160                                                                                 ##STR177##                          78   156  hydro- chloride                                                                       188                  161                                                                                 ##STR178##                          86        maleate                                                                               176                  162                                                                                 ##STR179##                          62        hydro- chloride                                                                       decomp.   >230       163                                                                                 ##STR180##                          57        methane- sulfonate                                                                    decomp. >230         164                                                                                 ##STR181##                          67        hydro- chloride                                                                       decomp. >220         165                                                                                 ##STR182##                          58        sulfate                                                                               decomp. >240         166                                                                                 ##STR183##                          71        hydro- chloride                                                                       decomp. >230         167                                                                                 ##STR184##                          52        hydro- decomp. >230         168                                                                                 ##STR185##                          67        hydro- chloride                                                                       decomp. >220         169                                                                                 ##STR186##                          82        methane- sulfonate                                                                    decomp. >240         170                                                                                 ##STR187##                                    hydro- chloride                                                                       decomp. >230         171                                                                                 ##STR188##                          61        hydro- chloride                                                                       decomp. >240         172                                                                                 ##STR189##                          69        hydro- chloride                                                                       decomp.              __________________________________________________________________________                                                               >220            

EXAMPLE 173

A solution of 9.1 gm of m-benzyloxy-ω-bromoacetophenone in 75 ml of ethanol was admixed at -5° C. with 1.2 gm of sodium borohydride, and the mixture was stirred for half an hour. The resulting solution was admixed with a little hydrobromic acid, the ethanol was distilled off under reduced pressure, and the residue was taken up in ethyl acetate. The solution was extracted first with an aqueous sodium bicarbonate solution and then with water, dried and evaporated in vacuo. The residue was taken up in 45 ml of dimethylformamide, admixed with 6.57 gm of 1-(4-amino-4,4-dimethylbutyl)-benzimidazolidinone-(2) and 6.65 gm of sodium carbonate, and the mixture was stirred for 6 hours at 105° C. After working up, the reaction product was isolated as its succinate of the formula ##STR190## which had a melting point of 94° C. The yield was 58% of theory.

Using an analogous procedure and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE III                                    __________________________________________________________________________     Ex.                                  Yield %                                                                              m.p. of       m.p. of               No. Formula                          of theory                                                                            Base °C.                                                                      Salt    Salt                  __________________________________________________________________________                                                              °C.            174                                                                                 ##STR191##                      61          p-amino- benzoate                                                                      166                   175                                                                                 ##STR192##                      59    68                                  176                                                                                 ##STR193##                      62          maleate 210                   177                                                                                 ##STR194##                      68          hydrochloride                                                                          239                   178                                                                                 ##STR195##                      76          p-amino benzoate                                                                       152.5                 179                                                                                 ##STR196##                      73          p-amino- benzoate                                                                      159                   180                                                                                 ##STR197##                      64    122                                 181                                                                                 ##STR198##                      64          sulfate 225                   182                                                                                 ##STR199##                      47    170   methane- sulfonate                                                                     185                   __________________________________________________________________________

EXAMPLE 183

By reacting 69.6 gm of the compound of the formula ##STR200## with 55.6 gm of chloroacetone in the presence of potassium carbonate and potassium iodide in acetone, followed by acidcatalyzed hydrolysis, 32 gm of the compound of the formula ##STR201## m.p. 182° C. were obtained. A solution of 19 gm of this substance in 300 ml of methanol was admixed with 25 ml of ammonia, and the mixture was hydrogenated with Raney nickel as the catalyst at 50° to 60° C. and 6 atmospheres. The hydrogenation product was isolated as its hydrochloride, m.p. 267°-270° C., of the formula ##STR202## The yield was 15.6 gm.

EXAMPLE 184

A mixture consisting of 35 gm of 3,4-dibenzyloxy-ω-bromoacetophenone, 24 gm of 1-(3-benzylamino-n-propyl)-benzimidazolinone-(2), 22 gm of sodium carbonate and 300 ml of acetonitrile was refluxed for 2 hours. The reaction product of the formula ##STR203## was isolated at its bioxalate with a yield of 44 gm (m.p. 168° C.). The free base (m.p. 112° C.) was liberated with aqueous ammonia. 35 gm of the base were dissolved in 350 ml of ethanol, 29 ml of 2 H sodium hydroxide were added to the solution, and then a total of 6 gm of sodium borohydride were added in portions over a period of 90 minutes. The reaction product of the formula ##STR204## was isolated as the free base (m.p. 93° C.).

A solution of 15 gm of the base in 150 ml of methanol was hydrogenated in the presence of 3 gm of palladized coal at 60° C. and 6 atmospheres until 3 molar equivalents of hydrogen had been absorbed. After removal of the catalyst, the solution was admixed with a solution of 2 gm of succinic acid in 20 ml of hot methanol, yielding 77% of theory of the crystalline succinate, m.p. 204° C., of the formula ##STR205##

Using analogous procedures and starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE IV                                     __________________________________________________________________________     Ex.                             Yield %                                                                             m.p. of     m.p. of                       No.                                                                               Formula                      of theory                                                                           Base °C.                                                                     Salt   Salt °C.               __________________________________________________________________________     183                                                                                ##STR206##                  81   170  methane- sulfonate                                                                    185                           186                                                                                ##STR207##                  77        succinate                                                                             189                           187                                                                                ##STR208##                  62        hydrochloride                                                                         185                           188                                                                                ##STR209##                  91        hydrochloride                                                                         198                           189                                                                                ##STR210##                  82        hydrochloride                                                                         182                           __________________________________________________________________________

EXAMPLE 190

A solution of 7 gm of the compound of the formula ##STR211## in 200 ml of methanol was hydrogenated in the presence of 1 gm of palladized coal under standard conditions until 2 molar equivalents of hydrogen had been absorbed. The hydrogenation product was isolated with a yield of 94% of theory as its maleate (m.p. 180° C., with 1 mol of water of crystallization) of the formula ##STR212##

Using analogous procedures and starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE V                                      __________________________________________________________________________     Ex.                                    Yield %                                                                              m.p. of     m.p. of               No. Formula                            of theory                                                                            Base °C.                                                                     Salt   Salt                  __________________________________________________________________________                                                              °C.            191                                                                                 ##STR213##                        91         hydrochloride                                                                         185                   192                                                                                 ##STR214##                        92         cyclamate                                                                             176                   193                                                                                 ##STR215##                        89         maleate                                                                               134                   194                                                                                 ##STR216##                        90         succinate                                                                             204                   195                                                                                 ##STR217##                        90         hydrochloride                                                                         170                   196                                                                                 ##STR218##                        85         hydrochloride                                                                         158                   197                                                                                 ##STR219##                        86         maleate                                                                               168                   198                                                                                 ##STR220##                        91         hydrochloride                                                                         265                   199                                                                                 ##STR221##                        90         hydrochloride × 2                                                        H.sub.2 O                                                                             275                   200                                                                                 ##STR222##                        85         maleate                                                                               180                   201                                                                                 ##STR223##                        91         maleate                                                                               157                   202                                                                                 ##STR224##                        94         maleate                                                                               136                   203                                                                                 ##STR225##                        83         succinate                                                                             176                   204                                                                                 ##STR226##                        93         p-amino- benzoate                                                                     193                   205                                                                                 ##STR227##                        92         succinate                                                                             171                   206                                                                                 ##STR228##                        93         succinate ×                                                              H.sub.2 O                                                                             128                   207                                                                                 ##STR229##                        92         succinate                                                                             215                   208                                                                                 ##STR230##                        90         hydrochloride                                                                         177                   209                                                                                 ##STR231##                        84         formate                                                                               214                   210                                                                                 ##STR232##                        90    190  hydrochloride                                                                         225                   211                                                                                 ##STR233##                        82         hydrochloride                                                                         170                   212                                                                                 ##STR234##                        93    193  hydrochloride                                                                         196                   213                                                                                 ##STR235##                        9          hydrochloride                                                                         175                   214                                                                                 ##STR236##                        94    206  hydrochloride                                                                         169                   215                                                                                 ##STR237##                        91    200  hydrochloride                                                                         201                   216                                                                                 ##STR238##                        86    198  hydrochloride                                                                         157                   217                                                                                 ##STR239##                        84         acid maleate                                                                          202                   218                                                                                 ##STR240##                        92         acid maleate                                                                          180                   219                                                                                 ##STR241##                        92    212  p-amino- benzoate                                                                     234                   220                                                                                 ##STR242##                        93    148  p-amino- benzoate                                                                     191                   221                                                                                 ##STR243##                        92         hydrochloride                                                                         190                   222                                                                                 ##STR244##                        86         succinate                                                                             189                   223                                                                                 ##STR245##                        84         formate × 1/2                                                            CH.sub.3 CN                                                                           159                   224                                                                                 ##STR246##                        89         hydrochloride                                                                         198                   225                                                                                 ##STR247##                        90         p-amino- benzoate                                                                     199                   226                                                                                 ##STR248##                        81         acid maleate                                                                          168                   227                                                                                 ##STR249##                        81         hydrochloride                                                                         230                   228                                                                                 ##STR250##                        84         hydrochloride                                                                         252                   229                                                                                 ##STR251##                        90         succinate                                                                             173                   230                                                                                 ##STR252##                        93    198  hydrochloride                                                                         235                   231                                                                                 ##STR253##                        85         succinate                                                                             212                   232                                                                                 ##STR254##                        82         succinate                                                                             218                   233                                                                                 ##STR255##                        84    180  hydrochloride                                                                         190                   234                                                                                 ##STR256##                        81         p-amino- benzoate                                                                     190                   235                                                                                 ##STR257##                        82    180  succinate                                                                             203                   236                                                                                 ##STR258##                        89         p-amino- benzoate                                                                     196                   237                                                                                 ##STR259##                        92    180  hydrochloride                                                                         193                   238                                                                                 ##STR260##                        82         hydrochloride                                                                         212                   239                                                                                 ##STR261##                        79         hydrochloride                                                                         182                   240                                                                                 ##STR262##                        79         hydrochloride                                                                         221                   241                                                                                 ##STR263##                        80    113  hydrochloride ×                                                          H.sub.2 O                                                                             80-82                 242                                                                                 ##STR264##                        75         formate                                                                               138                   243                                                                                 ##STR265##                        82         methane- sulfonate                                                             × H.sub.2                                                                       120                   244                                                                                 ##STR266##                        86         sulfate                                                                               192                   245                                                                                 ##STR267##                        88    173  hydrochloride                                                                         203                   246                                                                                 ##STR268##                        73.6  175  hydrochloride                                                                         216                   247                                                                                 ##STR269##                        63         hydrochloride                                                                         181                   248                                                                                 ##STR270##                        74    169  dihydro- chloride                                                                     206                   249                                                                                 ##STR271##                        72                                      250                                                                                 ##STR272##                        69         hydro- chloride                                                                       amorphous             251                                                                                 ##STR273##                        87    156  hydro- chloride                                                                       188                   252                                                                                 ##STR274##                        75         maleate                                                                               176                   253                                                                                 ##STR275##                        74         hydro- chloride                                                                       decomp.  >230         254                                                                                 ##STR276##                        92         methane- sulfonate                                                                    decomp. >230          255                                                                                 ##STR277##                        88         hydro- chloride                                                                       decomp. >220          256                                                                                 ##STR278##                        87         sulfate                                                                               decomp. >240          257                                                                                 ##STR279##                        78         hydro- chloride                                                                       decomp. >230          258                                                                                 ##STR280##                        80         hydro- chloride                                                                       decomp. >230          259                                                                                 ##STR281##                        78         hydro- chloride                                                                       decomp. >220          260                                                                                 ##STR282##                        72         methane- sulfonate                                                                    decomp. >240          261                                                                                 ##STR283##                        81         hydro- chloride                                                                       decomp.  >230         262                                                                                 ##STR284##                        69                                      __________________________________________________________________________

EXAMPLE 263

A mixture consisting of 3.9 gm of the compound of the formula ##STR285## 2 gm of acetic acid anhydride and 40 ml of dimethylformamide was heated on a boiling water bath for 1 hour. Thereafter, the solvent was distilled off in vacuo, and the base was liberated with ammonia, taken up in ethyl acetate, and the solution was dried. The ethyl acetate was distilled off, and the base was admixed in acetonitrile with the calculated amount of maleic acid, yielding 3.5 gm of the maleate of the formula ##STR286## which had a melting point of 202° C. after recrystallization from methanol.

EXAMPLE 264

A solution of 6.1 gm of the compound of the formula ##STR287## in a mixture of 20 ml of water and 7.5 ml of glacial acetic acid was admixed with a solution of 1.41 gm of potassium cyanate in 7.5 ml of water at 35° C. After standing overnight, the base was liberated with ammonia, separated by extracting it three times with isobutanol and converted into the maleate of the formula ##STR288## were obtained. After recrystallization from water, it had a melting point of 202° C.

EXAMPLE 265

A mixture consisting of 5 gm of the compound of the formula ##STR289## 100 ml of methanol and 100 ml of a concentrated aqueous ammonia solution was gently heated until a solution had formed. The solution was allowed to stand for an extended period of time, during which 4.3 gm of the base (m.p. 198° C.) of the formula ##STR290## crystallized out. Its hydrochloride, obtained by acidifying an ethanolic solution of the base with hydrochloric acid, had a melting point of 235° C.

Using analogous procedures and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE VI                                     __________________________________________________________________________     Ex.                                     Yield %                                                                             m.p. of     m.p. of               No.          Formula                    of theory                                                                           Base °C.                                                                       Salt Salt                  __________________________________________________________________________     266                                                                                ##STR291##                          83   172  hydrochloride                                                                         204                   267                                                                                ##STR292##                          86   113  hydrochloride ×                                                          H.sub.2 O                                                                             80-82                 268                                                                                ##STR293##                          84   180  hydrochloride                                                                         190                   269                                                                                ##STR294##                          84        hydrochloride                                                                         221                   270                                                                                ##STR295##                          91   190  hydrochloride                                                                         225                   271                                                                                ##STR296##                          86        hydrochloride                                                                         195                   272                                                                                ##STR297##                          83.5      hydrochloride                                                                         147                   273                                                                                ##STR298##                          77        hydrochloride                                                                         178 (decomp.)         274                                                                                ##STR299##                          95        hydrochloride                                                                         208 (decomp.)         275                                                                                ##STR300##                          90   145  hydrochloride                                                                         215 (decomp.)         276                                                                                ##STR301##                          88        hydrochloride                                                                         197 (decomp.)         277                                                                                ##STR302##                          63   157  hydro- chloride                                                                       137                   __________________________________________________________________________

EXAMPLE 278

69.6 gm of the compound of the formula ##STR303## and then a solution of 0.44 mol of 3-(dibenzylamino)-n-propyl chloride in 300 ml of absolute ethanol were added to a solution of 0.42 mol of sodium in 200 ml of absolute ethanol, and the mixture was refluxed for six hours. Thereafter, the precipitated sodium chloride was separated, and the liquid phase was admixed with 45 ml of concentrated sulfuric acid while stirring and cooling. After three hours 700 ml of water were added, the ethanol was distilled off, and the residual solution was made alkaline with ammonia, whereupon the compound of the formula ##STR304## precipitated out. Recrystallized from acetonitrile, the product had a melting point of 146° C.

60 gm of this compound were hydrogenated in a mxture of 400 ml of methanol and 200 ml of water in the presence of 16 ml of concentrated hydrochloric acid and palladized coal at 60° C. and 6 atmospheres until 1 molar equivalent of hydrogen had been absorbed. 88% of theory of the compound of the formula ##STR305## were obtained; it had a melting point of 60° C.

EXAMPLE 279

A solution of 53.4 gm of the compound of the formula ##STR306## in 420 ml of methanol and 80 ml of water was hydrogenated in the presence of 20 ml of concentrated hydrochloric acid and palladized coal at 60° C. and 6 atmospheres until 1 molar equivalent of hydrogen had been absorbed. 91% of theory of the hydrochloride (m.p. 315° C.) of the formula ##STR307## was obtained.

EXAMPLE 280

10.1 gm of sodium hydride and 45 gm of N-(3-chloro-n-propyl)-phthalimide were added to a solution of 31.1 gm of the compound of the formula ##STR308## in 150 ml of hexamethylphosphoric triamide (hexametapol) in an atmosphere of nitrogen, and the mixture was stirred for 5 hours at 100° C. The isolated raw reaction product of the formula ##STR309## was refluxed in 1 liter of ethanol with 13 gm of 85% hydrazine hydrate for 90 minutes, admixed with 21 ml of concentrated hydrochloric acid and 100 ml of water, and heated again for 20 minutes. The precipitated phthalic acid hydrazide was separated by suction filtration, and the hydrochloride (m.p. 195° C. from ethanol) of the formula ##STR310## was isolated.

EXAMPLE 281

3.3 gm of sodium hydride (55%) were added to a solution of 9.2 gm of the compound of the formula ##STR311## in 40 ml of absolute hexamethylphosphoric triamide in an atmosphere of nitrogen, and after the calculated amount of hydrogen had been released, a solution of 3-benzylamino-n-propyl chloride (b.p. 140° C. at 12 mm Hg) in 13 ml of hexamethylphosphoric triamide was added. The resulting mixture was stirred for 5 hours at 100° C., then poured over ice, and the reaction product of the formula ##STR312## was isolated by extraction with ether and hydrolyzed without purification with 2 N hydrochloric acid, yielding 67% of theory of the hydrochloride of the formula ##STR313## which had a melting point of 152°-155° C.

Using analogous procedures and corresponding starting compounds, the compounds shown in the following table were also prepared:

                                      TABLE VII                                    __________________________________________________________________________     Ex.                          Yield %                                                                             m.p. of    m.p. of                           No.                                                                               Formula                   of theory                                                                           Base                                                                               Salt   Salt °C.                   __________________________________________________________________________     282                                                                                ##STR314##               84.5 175 hydrochloride × H.sub.2                                                         280                               283                                                                                ##STR315##               54       hydrochloride                                                                         150                               284                                                                                ##STR316##               62       maleate                                                                               157                               285                                                                                ##STR317##               55       hydrochloride                                                                         214-216                           286                                                                                ##STR318##               90       hydrochloride                                                                         277-79                            287                                                                                ##STR319##               68       hydrochloride                                                                         237-239                           288                                                                                ##STR320##               75       hydrochloride                                                                         266-268                           289                                                                                ##STR321##               74   76  hydrochloride × H.sub.2                                                           140.5                           290                                                                                ##STR322##               92   135 hydrochloride                                                                         306                               291                                                                                ##STR323##               89       hydrochloride                                                                         253                               292                                                                                ##STR324##               65       p-amino- benzoate                                                                     245                               293                                                                                ##STR325##               70       p-amino- benzoate                                                                     225                               294                                                                                ##STR326##               82       p-amino- benzoate                                                                     233                               295                                                                                ##STR327##               80       hydrochloride                                                                         267-70                            296                                                                                ##STR328##               62       maleate                                                                               179                               297                                                                                ##STR329##               87   81                                           298                                                                                ##STR330##               75       hydrochloride                                                                         246                               299                                                                                ##STR331##               72.3     hydrochloride                                                                         185                               300                                                                                ##STR332##               61       hydrochloride                                                                         225                               301                                                                                ##STR333##               60       hydrochloride                                                                         202                               302                                                                                ##STR334##               89       hydrochloride                                                                         225                               __________________________________________________________________________

EXAMPLE 303

A solution of 174 gm of the compound of the formula ##STR335## in 700 ml of absolute hexamethylphosphoric triamide was admixed with 48 gm of sodium hydride in the form of a 55% suspension, and after the evolution of hydrogen had ceased, a solution of 341 gm of the compound of the formula ##STR336## (m.p. 76° C.) in 450 ml of hexamethylphosphoric triamide was added. The mixed solution was stirred for 5 hours at 100° C., then poured over ice, extracted with ether, and after evaporation of the ether from the extract the residue was dissolved in 3 liters of ethanol, and the solution was admixed with 300 ml of 5 N sulfuric acid. The next day the reaction product of the formula ##STR337## was isolated with a yield of 61% of theory (m.p. 198° C.). 58.75 gm of this compound were dissolved in 1700 ml of methanol, and after addition of Raney nickel the solution was hydrogenated at 6 atmospheres and 40°-60° C. The compound of the formula ##STR338## was isolated with a yield of 92% of theory (m.p. 135° C.).

Its hydrochloride had a melting point of 306° C.

The compounds of the present invention, that is, those embraced by formula I above and their non-toxic, pharmacologically acceptable acid addition salts, have useful pharmacodynamic properties. More particularly, they exhibit coronary dilating and CNS-stimulating activities in warm-blooded animals, such as rats, guinea pigs and dogs, and are therefore useful as antihypertensives, bronchopasmolytics, circulation enhancers and antidepressants.

When R in formula I is a substituent group of the formula III, the nature of the variable substituents on the phenyl moiety thereof has an effect on the predominant pharmacological activity of these compounds.

For example, when R₅, R₆ and R₇ are lipophilic radicals or impart a lipophilic character to the substituent group of the formula III, the antidepressant activity predominates in these compounds. Such is the case, for instance, when R₅, R₆ and R₇ are hydrogen, halogen, alkoxy, amino, alkyl or trifluoromethyl, or when R₇ is hydrogen and R₅ and R₆ together with each other are ethylenedioxy or especially methylenedioxy.

When R₅, R₆ and R₇ are -OR₈ (where R₈ is hydrogen, acyl or aralkyl), --NH-acyl, amino or hydroxymethyl, or when R₅ and R₆ together with each other are --O--CH₂ --CONH--, --CH₂ --CH₂ --CONH-- or --O--CONH-- and R₇ is hydroxyl, the vasodilating activity predominates in these compounds.

Finally, when R₅ is --OR₈ (where R₈ is hydrogen, acyl or aralkyl), R₆ is --CONHR₃ and R₇ is especially hydrogen, the antihypertensive activity predominates in these compounds.

Illustrative of the good pharmacological activity of the compounds of the present invention are the following data where ##STR339##

Compound B, tested for peripheral vasodilation in dogs by measurement of the blood flow through the left hind extremity after intra-arterial administration, had a 22 times longer effective half-time and was 18 times more effective than the known vasodilator isoxsuprine.

Compound A, tested for antihypertensive activity on awake, genetically hypertonic rats, produced a decrease in blood pressure of 85 mm Hg at a dosage level of 30 mgm/kg i.p.

Compound C, tested for bronchospasmolytic activity in guinea pigs, was found to have a median effective dose ED₅₀ i.v. of 0.09 μgm/kg, whereas the corresponding ED₅₀ - value for the known, highly effective bronchospasmolytic isoproterenol is 3.0 μgm/kg.

For pharmaceutical purposes the compounds according to the present invention are administered to warm-blooded animals perorally, parentereally, rectally or by the inhalation route as active ingredients in customary dosage unit compositions, that is, compositions in dosage unit form consisting essentially of an inert pharmaceutical carrier and one effective dosage unit of the active ingredient, such as tablets, coated pills, capsules, wafers, powders, solutions, suspensions, emulsions, syrups, suppositories, inhalation sprays and the like. One effective dosage unit of the compounds according to the present invention is from 0.016 to 8.33 mgm/kg body weight, preferably 0.033 to 3.3 mgm/kg body weight, depending upon the form or mode of administration and the particular compound. The higher dosages are primarily adapted for sustained release compositions.

The following examples illustrate a few pharmaceutical dosage unit compositions comprising a compound of the present invention as an active ingredient and represent the best modes contemplated of putting the invention into practical use. The parts are parts by weight unless otherwise specified.

EXAMPLE 304

Tablets

The tablet composition is compounded from the following ingredients:

    ______________________________________                                         1-(3,4-Methylenedioxy-phenyl)-2-[1,1-                                          dimethyl-3-(benzimidazolidin-2-one-                                            1-yl)-n-propyl-amino]-ethanol maleate                                          (see Example 55)         2      parts                                          Stearic acid             6      parts                                          Glucose                  592    parts                                          Total                    600    parts                                          ______________________________________                                    

Preparation:

The ingredients are admixed in conventional manner, and the composition is compressed into 600 mgm-tablets. Each tablet contains 2 mgm of the active ingredient and is an oral dosage unit composition.

EXAMPLE 305

Suppositories

The suppository composition is compounded from the following ingredients:

    ______________________________________                                         1-(3,4-Methylenedioxy-phenyl)-2-[1,1-                                          dimethyl-3-(3-methylbenzimidazolidin-                                          2-one-1-yl)-n-propyl-amino]-ethanol                                            hydrochloride (see Example 63)                                                                          100    parts                                          Lactose, powdered        45     parts                                          Cocoa butter             1555   parts                                          Total                    1700   parts                                          ______________________________________                                    

Preparation:

The ingredients are processed in conventional manner into 1700 mgm-suppositories, each of which contains 100 mgm of the active ingredient and is a rectal dosage unit composition.

EXAMPLE 306

Capsules

The capsule filler composition is compounded from the following ingredients:

    ______________________________________                                         1-(3-Carboxymethylamido-4-hydroxyphenyl)-                                      2-[1,1-dimethyl-3-(1,2,3,4-tetrahydro-                                         quinol-2-one-1-yl)-n-propyl-amino]-                                            ethanol hydrochloride (see Example 233)                                                                  200    parts                                         Lactose                   440    parts                                         Corn starch               360    parts                                         Total                     1000   parts                                         ______________________________________                                    

Preparation:

The ingredients are intimately admixed, the mixture is milled into a powder, and 1000 mgm-portions of the powder are filled into gelatin capsules of suitable size. Each capsule is an oral dosage unit composition containing 200 mgm of the active ingredient.

Any one of the other compounds embraced by formula I or a non-toxic, pharmacologically acceptable acid addition salt thereof may be substituted for the particular active ingredient in Examples 304 through 306. Likewise, the amount of active ingredient in these illustrative examples may be varied to achieve the dosage unit range set forth above, and the amounts and nature of the inert pharmaceutical carrier ingredients may be varied to meet particular requirements.

While the present invention has been illustrated with the aid of certain specific embodiments thereof, it will be readily apparent to others skilled in the art that the invention is not limited to these particular embodiments, and that various changes and modifications may be made without departing from the spirit of the invention or the scope of the appended claims. 

We claim:
 1. A racemic or optically active compound of the formula

    Q--C.sub.n H.sub.2n --NH--R

wherein Q is ##STR340## where R₁ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino, R₂ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or trifluoromethyl, or R₁ and R₂, together with each other, are methylenedioxy or ethylenedioxy; n is an integer from 2 to 6, inclusive; and R is hydrogen, benzyl or ##STR341## where R₄ is hydrogen, methyl or ethyl, R₅, R₆ and R₇, which may be identical to or different from each other, are each hydrogen, halogen, hydroxymethyl, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, cyano, --CONHR₃, --CONHOH, --COOR₃, R₈ O--, methylsulfonylmethyl or, when one or two of R₅ through R₇ are other than halogen or trifluoromethyl, also --NR₃ R₉,where R₃ is hydrogen or alkyl of 1 to 4 carbon atoms, R₈ is hydrogen, alkanoyl of 1 to 20 carbon atoms, alkyl of 1 to 4 carbon atoms or phenyl(C₁₋₄)alkyl and R₉ is hydrogen, lower alkanoyl, methanesulfonyl, carbamoyl, dimethylsulfamoyl, or alkoxycarbanoyl of 2 to 5 carbon atoms, with the proviso that R₅, R₆, and R₇ cannot all be tert.butyl, or R₅ and R₆, together with each other are --O--CH₂ --O--, --O--CH₂ CH₂ --O--, --CH═CH--CH═CH--, --O--CH₂ --CONH--, or --O--CO-NH,or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 2. A compound of claim 1, which is 1-(β-naphthyl)-2-(1,1-dimethyl-3-benzoxazolonyl-n-propyl-amino)-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 3. A compound of claim 1, which is 1-(2-methyl-3,4-dibenzyloxy-phenyl)-2-(1,1-dimethyl-3-benzoxazolonyl-n-propyl-amino)-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 4. A compound of claim 1, which is 1-(3,4-methylenedioxy-phenyl)-2-(1,1-dimethyl-3-benzoxazolonyl-n-propylamino)-ethanol or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 5. A racemic or optically active compound of the formula

    Q--C.sub.n H.sub.2n --NH--R

wherein Q is ##STR342## where R₁ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, trifluoromethyl or amino, R₂ is hydrogen, halogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or trifluoromethyl, or R₁ and R₂, together with each other, are methylenedioxy or ethylenedioxy; n is an integer from 2 to 6, inclusive; and R is hydrogen, benzyl or ##STR343## where R₄ is hydrogen, methyl or ethyl, R₅ and R₆, which may be identical to or different from each other, are each hydrogen, halogen, hydroxymethyl, methyl, or R₈ O--, wherein R₈ is hydrogen, alkanoyl of 1 to 20 carbon atoms, alkyl of 1 to 4 carbon atoms, or benzyl or R₅ and R₆, together with each other are --O--CH₂ --O--, --O--CH₂ CH₂ --O--, --CH═CH--CH═CH--, --O--CH₂ --CONH--, or --O--CO--NH--,and R₇ is hydrogen, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, nitro, cyano, trifluoromethyl, --CONHR₃, --CONHOH, --COOR₃, methylsulfonylmethyl, or, when at least one of R₅ and R₆ is other than halogen, also --NR₃ R₉,where R₃ is hydrogen or alkyl of 1 to 4 carbon atoms and R₉ is hydrogen, lower alkanoyl, methanesulfonyl, carbamoyl, dimethylsulfamoyl, or alkoxycarbanoyl of 2 to 4 carbon atoms,or a non-toxic, pharmacologically acceptable acid addition salt thereof.
 6. A vasodilating or antidepressant pharmaceutical dosage unit composition consisting essentially of an inert pharmaceutical carrier and an effective vasodilating or anti-depressant amount of a compound of claims 1 or
 5. 7. The method of dilating the blood vessels or relieving depression in warm-blooded animal in need thereof, which comprises perorally, parenterally or rectally administering to said animal an effective vasodilating or anti-depressant amount of a compound of claims 1 or
 5. 8. A vasodilating or anti-depressant pharmaceutical dosage unit composition consisting essentially of an inert pharmaceutical carrier and an effective vasodilating or anti-depressant amount of a compound of claim
 2. 9. The method of dilating the blood vessels or relieving depression in a warm-blooded animal in need thereof, which comprises perorally, parenterally or rectally administering to said animal an effective vasodilating or anti-depressant amount of a compound of claim
 2. 10. A vasodilating or anti-depressant pharmaceutical dosage unit composition consisting essentially of an inert pharmaceutical carrier and an effective vasodilating or anti-depressant amount of a compound of claim
 3. 11. The method of dilating the blood vessels or relieving depression in a warm-blooded animal in need thereof, which comprises perorally, parenterally or rectally administering to said animal an effective vasodilating or anti-depressant amount of a compound of claim
 3. 12. A vasodilating or anti-depressant pharmaceutical dosage unit composition consisting essentially of an inert pharmaceutical carrier and an effective vasodilating or anti-depressant amount of a compound of claim
 4. 13. The method of dilating the blood vessels or relieving depression in a warm-blooded animal in need thereof, which comprises perorally, parenterally or rectally administering to said animal an effective vasodilating or anti-pressant amount of a compound of claim
 4. 